A Confounding Condition – Treating Chronic Fatigue Syndrome & Fibromyalgia

March 30, 2022

driveyourgrowth@gmail.com
2 Comments

When it comes to treating patients with chronic fatigue syndrome (CFS) and fibromyalgia (FM), doctors are often at a loss. Because they can’t figure out what’s wrong, many consider CFS and FM “wastebasket” diagnoses. Others simply dismiss the symptoms as psychiatric in nature.1-3

This certainly is a disservice to the estimated 4 percent to 7 percent of the population that suffers from these conditions. These disorders, which strike women four times as much as men,1-3 are consistently associated with a unique set of physiologic abnormalities.4-71

Physicians need to employ a multisystem approach, instead of resorting to single-drug modalities for each symptom.12,16,72-87 This comprehensive approach is largely becoming the standard of care and is effective in 80 percent of patients with these conditions.

What is Fibromyalgia?

To be diagnosed with FM, patients must experience pain for at least three months. They also must feel pain upon palpation at 11 out of 18 tender points.88 This criteria, however, is criticized for not taking into account the essential elements of FM, such as fatigue, sleep disturbance, and cognitive dysfunction.89-93

For a CFS diagnosis, patients must experience fatigue that doesn’t improve with bed rest. This fatigue should impair the average daily activity level by more than 50 percent for at least six months. People also must experience four or more of the following symptoms: cognitive dysfunction, sore throat, joint pain, muscle pain, headaches, non-refreshing sleep, and post-exertional malaise.94

Furthermore, there’s no accepted laboratory marker to define these conditions. Consequently, physicians have difficulty properly diagnosing FM and CFS. But despite different modes of diagnosis (physical exam vs. history), CFS and FM share numerous common dysfunctions and coexist 50 percent to 70 percent of the time, depending on the study. Therefore, from a clinical standpoint, we will consider these illnesses together. The range of symptoms in these conditions includes fatigue, sleep disturbances, muscle pain, cognitive dysfunction, gastrointestinal dysfunction, headaches, and post-exertional malaise.

Note that the unique physiologic hallmarks of CFS and FM don’t exist in other fatiguing illnesses 4-71. These syndromes are complicated, involving pituitary and hypothalamic dysfunction, immune dysfunction, sleep stage disorder, mitochondrial dysfunction, hormonal deficiencies, coagulation defects and chronic infections.

In addition, each physiologic abnormality can cascade into other problems. For example, chronic stress can produce hypothalamic, pituitary and immune dysfunction—signature signs of fibromyalgia. Immune dysfunction can reactivate viral and intracellular bacterial infections. This can further suppress hypothalamic and pituitary function, causing mitochondrial dysfunction and coagulation dysregulation.

Hypothalamic and pituitary dysfunction produces hormonal deficiencies. In a vicious cycle, chronic infections can further suppress mitochondrial function and produce global cellular dysfunction and a subsequent immune activation that causes a coagulation defect. This, in turn, worsens cellular function. This cascade produces multi-system illness that causes a broad range of often perplexing symptoms.

The Multi-system Approach

CFS and FM diagnoses often frustrate physicians because there’s no clear cause or treatment. Doctors typically treat the problem with NSIADs, antidepressants and muscle relaxants. But these drugs are largely ineffective because they fail to address the underlying causes of the problem 95-109. In addition, they have a high incidence of significant side effects, including anxiety and insomnia 95,69. Muscle relaxants, too, can be addictive. Serotonin-norepinephrine reuptake inhibitors (SNRIs) and anticonvulsants may offer some benefit (Pregabalin is the first medication that is FDA approved to treat FM), but they’re often ineffective. In addition, the majority of patients don’t tolerate the medication well.

Given these facts, physicians should take the following multi-system approach to address both diagnoses.

COMPONENT ONE:

Stabilize the Patient

Physicians commonly address the pain and sleep disturbances of CFS and FM with medications. These drugs can help some patients, but the overwhelming majority need further treatment. Sadly, this first stage of treatment is the only course many doctors prescribe.

Not only do the reduced amounts of metabolized glucose produce weight gain, reduced aerobic energy production requires the body to rely on anaerobic metabolism. This causes fatigue, muscle pain, poor concentration, gastrointestinal dysfunction, headaches, and postexertional malaise.

Mitochondria can be poisoned by numerous substances, including environmental toxins, pesticides, chronic bacterial, viral, and fungal infections, neurotoxins, and nutritional and hormone deficiencies. Mitochondria dysfunction has the greatest impact on the most active tissues, including the hypothalamus, pituitary, muscle, nerve and immune cells. These are the major dysfunctions of these conditions and can significantly explain the symptoms of CFS/FM. Supplying mitochondrial intermediates and nutrients, such as magnesium, carnitine, D-ribose, CoQ10 and glutathione can improve mitochondrial function and alleviate symptoms of CFS and FM.111-116

COMPONENT TWO:

Mitochondrial Enhancement.

The mitochondria are the energy factories for the cells where sugar is burned and energy is produced in the form of adenosine-tri-phosphate (ATP). When the mitochondria are not working properly, the cells and tissues of the body are starved for energy. This abnormality may be the common endpoint for all the dysfunctions in CFS and FM.

Mitochondria can be poisoned by numerous substances, including environmental toxins, pesticides, chronic bacterial, viral and fungal infections, neurotoxins and nutritional and hormone

deficiencies. Mitochondria dysfunction has the greatest impact on the most active tissues, including the hypothalamus, pituitary, muscle, nerve and immune cells. These are the major dysfunctions of these conditions and can significantly explain the symptoms of CFS/FM. Supplying mitochondrial intermediates and nutrients, such as magnesium, carnitine, D-ribose, CoQ10 and glutathione, can improve mitochondrial function and alleviate symptoms of CFS and FM.111-116

COMPONENT THREE:

Balance the Hormones

An overwhelming amount of peer-reviewed medical literature documents pituitary and hypothalamic dysfunction CFS and FM patients. As a result, patients often have multiple hormonal deficiencies 4-21, including thyroid, growth hormone and cortisol. Physicians often miss these hormonal deficiencies because standard blood tests lack sufficient sensitivity to detect such centrally mediated deficiencies 4,5,6,7,17-21-. However, they need to pay close attention to the following hormones:

Thyroid. Numerous studies have demonstrated that central hypothyroidism as well as cellular resistance to thyroid hormone exists in the overwhelming majority of patients with FM and CFS. This persists, despite their having normal thyroid function tests (TFTS) 6,11-16.

For instance, a study published in the journal of Rheumatology looked at the incidence of central hypothyroidism in patients with FM. Through thyrotropin-releasing hormone (TRH) testing, all of the patients with FM had central hypothyroidism, despite having baseline TFTs in the normal range. More than 90 percent of the time, standard TSH and T4 testing misses central mediated hypothyroidism 117.

Emerging evidence, however, shows free T3/reverse T3 (rT3) ratios can be a useful indicator of tissue thyroid levels. This may, in fact, help physicians assess tissue thyroid effect with central hypothyroidism and chronic physiologic stress 118-120. Instead of T4 normally converting intracellularly to the active T3 in peripheral tissue, T4 is preferentially converted to reverse T3. Therefore, increasing levels of rT3 and diminishing levels of T3 are indicators of low tissue thyroid effect. Free T3 and rT3 tests can be ordered at most major clinical laboratories. A free T3/rT3 ratio that’s less than 2 pg/ng is consistent with low tissue thyroid activity.

Because T4 to T3 conversion in these conditions is diminished, it’s not surprising that T4 supplementation has little effect, but that treatment with T3 is significantly effective.

In a double-blinded, placebo-controlled trial by Lowe, et al., T3 therapy was safe and effective for treating euthyroid (TFTs in the normal range) FM. Patients reported a highly significant improvement in pain, fatigue, stiffness, head-ache, sleep disturbance, bowel disturbance, depression, cognitive dysfunction, anxiety, cold intolerance, paresthesias and exercise endurance. They noted no significant adverse effects, despite having TFTs that would normally indicate hyperthyroidism, with a suppressed TSH, low free T4 and high free T3 levels. No adverse effects were reported on heart, bone muscle and liver function, which were monitored every two months for eight months.

In a small, double-blinded, placebo-controlled crossover study of four patients, T3 was administered and withdrawn in two T3 phases and two placebo phases over nine months.118 All patients had normal baseline TFTs. All significantly improved in the T3 phases and deteriorated during placebo phases. No adverse target tissue effects were seen and all patients chose to continue treatment after the study’s end. This study did not demonstrate any adverse cardiac or bone effects.

T3 is available as the brand Cytomel or as a compounded timed-released preparation, which has the advantage over Cytomel in minimizing serum fluctuations of T3. Optimal doses can vary significantly among patients and should be slowly titrated with careful monitoring for signs of excess, such as palpitations, rapid heart rate, and anxiety.

Cortisol. Most patients with CFS and FM suffer from clinically significant adrenocortical dysfunction due to hypothalamic and pituitary dysfunction. The hypothalamic and pituitary function in these conditions (potentially due to mitochondrial function) results in inadequate cortisol production.

All studies that have used central acting stimulation testing in CFS and FM have shown signifi-

cant hypothalamic-pituitary-adrenal (HPA) axis dysfunction.4 However, physicians often believe a normal serum cortisol level or ACTH stimulation test generally rules out significant HPA axis dysfunction. These tests are much more useful for primary hypoadrenalism. They, however, lack sufficient sensitivity to detect the central HPA axis dysfunction.4

The current evidence supports using physiologic doses of cortisol as an appropriate component of a multi-system treatment protocol for CFS and FM. Specialists should consider a therapeutic trial of cortisol in the majority of these patients, especially those with signs or symptoms consistent with adrenal dysfunction, low blood pressure and/or serum levels that are low or in the low-normal range.

Physiologic replacement of cortisol at doses of 5mg to 15mg a day are safe, with little or no associated risk.Such physiologic doses don’t carry the risk of adrenal and immune suppression or bone loss, which are well known risks of pharmacological doses of corticosteroids.Cortisol treatment carries significantly less risk and greater potential for benefit than standard treatments, such as anti-depressants, muscle relaxants, anticonvulsants and narcotics 4.

Growth Hormone. Studies also show CFS and FM patients have diminished secretion of growth hormone secretion, a single-chain poly- peptide produced in the pituitary gland with a wide range of metabolic and cellular effects. Growth hormone stimulates the production of insulin-like growth factor-1 (IGF-1) in the liver. Both play an important role in regulating body composition, lipid profiles, tissue repair, cardiac and neuronal functioning and bone mineral density. A great deal of peer-reviewed research, including long-term randomized control trial data, has demonstrated that growth hormone replacement can improve energy, strength, cardiac function, cognitive function, immunity and psychological well-being. It also decreases body fat, increases lean muscle and improves quality of life. It also significantly improves symptoms in these conditions with little or no side effects.7-21,124

Because of the pulsatile nature of growth hormone production and short half-life (20 to 50 minutes), routine serum growth hormone levels cannot be used to determine overall pro- duction. However, IGF-1 levels correlate with overall growth hormone production and are relatively stable in the serum. While a normal IGF-1 level doesn’t rule out a significant growth hormone deficiency, the IGF-1 level is the best estimate of growth hormone production and effect. Low-normal IGF-1 levels are consistent with a relative growth hormone deficiency.

Titrating the dose of growth hormone to achieve IGF-1 levels in the upper limit of normal is safe, well tolerated and offers significant clinical benefits. Typical doses are 0.5-2 iu injected subcutaneously daily. Patients can start with a three-month therapeutic trial. We must monitor for water retention, which can produce joint pain and carpal tunnel syndrome. Insulin sensitivity may temporarily decline as well. Such treatment is generally well tolerated and if such side effects do occur, they usually resolve with a reduction in dose. Because of the synergistic nature of hormones, small doses of multiple hormones are generally superior to large doses of any one hormone. Each hormone, however, should be started one at a time so we can best monitor for potential side effects.

COMPONENT FOUR

Treat the Infectious Component

A great deal of medical literature documents the multiple infections that may either cause or contribute to CFS and FM.39-48,125-128 Likely, this is due to the immune dysfunction seen with these conditions, which allows opportunistic organisms and other infections to flourish. This includes a variety of viruses such as Epstein Barr (EBV), cytomegalovirus (CMV), human herpes virus 6 (HHV6) and intracellular bacterial infec- tions, such as mycoplasma, Chlamydia pneumonia and Borrelia burgdorferi (Lyme disease). Various antimicrobial treatments directed at such infections are significantly beneficial.

COMPONENT FIVE

Address Unique Etiologies

Several cycles of dysfunction occur in these conditions that can produce unique pathologi- cal etiologies. For instance, chronic infections can cause an abnormal immune activation of coagulation. This produces a fibrin coating on the lumen of the vessel, causing impaired oxygen and nutrient transfer. Fatigue, muscle aches and cognitive dysfunction.2,57-62 If suspected, the diagnosis can be made by testing a coagulation panel of soluble fibrin monomer, thrombin-antithrombin complex, D-dimer and plasminogen activator-inhibitor-1.57-62 Heparin can help such patients.12,58

Evidence also suggests that neurotoxins are a potential cause or contributing factor to CFS and FM symptoms.129-131 Visual contrast sensitivity testing and serum C3(a) and C4(a) can help us assess the potential for such exposure.

COMPONENT SIX

Maintenance

We need to adjust therapies and wean them to minimal core treatments. With improvement, medications can be discontinued, generally one at a time. During this phase, patients can be seen less often. We generally wean patients off medications before supplements. We also can successfully take patients off narcotic pain relievers. Symptomatic improvement usually correlates with improved cortisol, growth hormone and thyroid levels—so we can adjust hormones as well. However, most patients feel better with the optimal supplemented thyroid levels. Continued thyroid supplementation also appears to prevent relapses.

Multisystem Efficacy

A multi-system approach is becoming the standard of care for patients with CFS and FM. And studies are backing this approach. For example, Teitelbaum et al. performed a randomized, double-blinded, placebo-controlled, intent-to- treat study on 72 FM/CFS patients. The goal was to assess the effectiveness of an integrative treatment approach that simultaneously treated the nutritional deficiencies, chronic infections and hormonal dysfunctions that exist with these conditions.72

Overall, 90 percent of patients had significant improvements vs. placebo in visual analog scores (p < 0.0002), the Fibromyalgia Impact Questionnaire (p <0.0005), the tender point index (p < 0.0001) and overall response (p < 0.0001) with no significant reported side effects.

The Journal of Chronic Fatigue Syndrome recently reported our center’s novel use of a com- puterized symptom assessment that evaluated the multisystem treatment protocol for more than 500 consecutive patients with CFS and FM.4 Ninety-four percent of patients had overall improvement by the fourth visit, with 75 percent noting significant overall improvement and 62 percent reporting substantial overall improvement. In subsequent visits, the majority of patients continued to improve. The average energy level more than doubled by the fourth visit, going from an average of 2.98 at baseline to 6.39, and then to 6.77 and 7.67 at the seventh and ninth visits, respectively. The average sense of well-being more than doubled by the fourth visit, increasing from a baseline average of 3.03 then to 6.29, 7.45 and 6.83 on the fourth, seventh and ninth visit, respectively.

Subsequently, more than 40 physicians were trained to use a simplified treatment algorithm at 17 centers across the country. This multicenter study included more than 4,000 consecutive CFS and FM patients who were treated with this simplified algorithm and tracked via the same computerized patient assessment system. Eighty- five percent of patients improved by the fourth visit, with 56 percent and 40 percent reporting significant and substantial improvement by the fourth visit. By the seventh visit, 62 percent of patients reported significant improvement, and 46 percent indicated substantial improvement.87 By addressing the multiple physiologic abnormalities that occur with CFS and FM, we can give our patients hope for dealing with these debilitating disorders.

—

KENT HOLTORF, MD, is an expert in treating chronic fatigue syndrome, fibromyalgia, complex endocrine dysfunction and chronic infections (including EBV, HHV6 and Lyme disease).

Dr. Holtorf received his doctorate of medicine from St. Louis University with residency training at UCLA. He has personally trained numerous physicians across the country to effectively treat chronic fatigue syndrome, fibromyalgia and chronic infectious diseases. Additionally, Dr. Holtorf was the founding medical director and developed the protocols for Fibromyalgia and Fatigue Centers and other centers across the country.

Disclosure Dr. Holtorf indicates that he has no affiliations with any commercial entities, directly or indirectly referenced in this article.

RESOURCES

1. Ehrlich GE. Pain Is Real; Fibromyalgia Isn’t. J Rheumatol. 2003 Aug;30(8):1666-7.

2. Wolfe F. Stop Using the American College of Rheumatology Criteria in the Clinic. J Rheuma- tol 200;30:8:1671-2.

3. Smythe H. Fibromyalgia Among Friends. J Rheumatol. 2004 Apr;31(4):627-30.

4. Holtorf K. Diagnosis and Treatment of Hypo- thalamic-Pituitary-Adrenal (HPA) Axis Dysfunc- tionin Patients with Chronic Fatigue Syndrome (CFS) and Fibromyalgia (FM). J Chronic Fatigue Syndrome 2008;14(3):59-88.

5. Riedel W, Layka H, Neeck. Secretory pattern of GH, TSH, thryoid hormones, ACTH, cor- til, FSH, and LH in patients with fibromyalgia syndrome following systemic injection of the relevant hypothalamic-releasing hormones. Z Rheumatol 1998;57:81-87.

6. Neeck G, Riedel. Thyroid Function in Patients with Fibromyalgia Syndrome. J Rheumatology 1992;19(7): 1120-1122.

7. Neeck G, Riedel W. Hormonal Perturbations in Fibromyalgia Syndrome. Annals New York Academy of Sciences 1999; 876:325-339.

8. Simons DG, Travell JG. Myofacial pain syn- dromes, perpetuation factors. In Textbook of Pain. P.D. Wall & R. Malzak, Eds.1989:369-385.

9. McCain GA, Tilbe AK. Diurnal hormone variation in fibromyalgia syndrome: A com- parison with rheumatoid arthritis. J Rheumatol 1989;16 (Supp19):154-157.

10. Ferraccioli G, Cavalieri F, Salaffi F, Fontana S, Scita F, Nolli M, Maestri D. Neuroendocri- nologic findings in primary fibromyalgia and in other rheumatic conditions. J. Rheumatol 1990;17:869-873.

11. Englebienne P, Verhas M, Herst CV, Ke Meirleir K. Type I interferons induce proteins susceptible to act as thyroid receptor (TR) corepressors and to signal the TR for destruc- tion by the proteasome: possible etiology for unexplained chronic fatigue. Med Hypoth 2003;60(2):175-180.

12. Garrison RL, Breeding PC. A metabolic ba- sis for fibromyalgia and its related disorders: the possible role of resistance to thyroid hormone. Medical Hypoth 2003;61(2):182–189.

13. Cullum ME et al. Mutations in the cerbAB1 gene: do they underlie euthyroid fibromyalgia. Medical Hypotheses 1997;48:125-135.

14. Lowe JC. Thyroid status of 38 Fibromyalgia Patients: Implications for the Etiology of Fi- bromyalgia. Clin Bulletin Myofascial Therapy 1997;2(1):47-64.

15. Lowe JC, Reichman AJ, Honeyman GS, Yellin J. Thyroid Status of Fibromyalgia Patients. Clin Bulletin Myofascial Therapy 1998;3(1):69-70.

16. Lowe JC. The Metabolic Treatment of Fi- bromyalgia. Ed Yelin JC. McDowell Publishing Company 2000.

17. Bennett RM, Clark SR, Campbell SM, Burck- hardt CS. Low levels of somatomedin C in pa- tients with fibromyalgia syndrome. A possible link between sleep and muscle pain. Arthritis and Rheumatism 1992;35(10):1113-1110.

18. Bennett RM, Cook DM, Clark SR, Burck- hardt CS, Campbell SM: Hypothalamic-pitu- itary-insulin-like growth factor-I axis dysfunc- tion in patients with fibromyalgia. J.Rheumatol. 1997; 24:1384-1389.

19. Bennett R. Growth Hormone in Musculo- skeletal Pain States. Current Pain and Headache Reports 2005; 9:331-338.

20. Bennett RM. Disordered growth hormone secretion in fibromyalgia: a review of recent findings and a hypothesized etiology. Z Rheu- matol 1998;57(Supp 2): 72-6.

21. Bennett RM, Clark SR, Walczyk J: A random- ized, double-blind, placebo-controlled study of growth hormone in the treatment of fibromyal- gia. Am J Med 1998;104:227-231.

22. Behen WH, More IR, Behan PO. Mitochon- drial abnormalities in postviral fatigue syn- drome. Acta Neuropathol 1991;83:61-65.

23. Pillemer S, Bradley LA, Crofford LJ, Mold- ofsky H, Chrousos GP. The Neuroscience and Endocrinology of FMS-[An NIH] Conference Summary. Arthritis & Rheumatism 1997;40 (11):1928-1939.

24. Drewes AM, Nielson KD, Taagholt SJ, Bjerre- gaard K, Svendson L, Gade J. Slow Wave Sleep in FMS. J. Musculoskeletal Pain 1995;3(Supp1):29.

25. Scharf MB, Baumann M, Berkowitz D. The effects of sodium oxybate on clinical symptoms and sleep patterns in patients with Fibromyalgia. J. Rheumatology 2003;30:1070-4.

26. Moldofsky H. Sleep and musculoskeletal pain. Am J Med 1986;81:85-9.

27. Moldofsky H. Sleep and fibrositis syndrome. Rheum Dis Clin North Am 1989;15:91-103.

28. Moldofsky H. The contribution of sleep- wake physiology to fibromyalgia. Adv Pain Res Ther 1990;17:227–240.

29. Klimas NG et al. Immunologic Abnormali- ties in Chronic Fatigue Syndrome J Clin Micro- biology 1990;28(6):1403-1410.

30. Peterson, A. L. Komaroff, and J. Ritz. Pheno- typic and functional deficiency of natural killer cells in patients with chronic fatigue syndrome. J. Immunol 1987;139:3306-3313.

31. Fletcher MA, Maher KJ, Klimas NG. Natural killer cell function in chronic fatigue syndrome 2002;2(2):129-139.

32. Ojo-Amaize EA, Conley EJ, Peter JB. Decreased natural killer cell activity is as- sociated with severity of chronic fatigue im- mune dysfunction syndrome. Clin Infect Dis 1994;18(Supp 1):S157-9.

33. Komaroff A. The biology of Chronic Fatigue Syndorme. Am. J Med 2000;108:169-71.

34. Suhadolnik RJ et al. Changes in the 2-5A syn- thetase/RNase L antiviral pathway in a controlled clinical trial with poly (I) poly(C12U) in chronic fatigue syndrome. In Vivo. 1994;8:599-604.

35. Suhadolnik RJ et al. Upregulation of the 2-5A synthetase/ RNase L antiviral pathway as- sociated with chronic fatigue syndrome. Clin Infect Dis 1994;18:S96-S104.

36. Suhadolnik RJ et al. Biochemical evidence for a novel low molecular weight 2-5A-depen- dent RNase L in chronic fatigue syndrome. J In- terferon & Cytokine Res1997;17:377-85.

37. Suhadolnik RJ et al. Biochemical dysregula- tion of the 2-5A synthetase/RNase L antiviral defense pathway in chronic fatigue syndrome. J Chronic Fatigue Syndrome.1999;5:223-242.

38. De Meirleir K et al. A 37 kDa 2-5A bind- ing protein as a potential biochemical mark- er for chronic fatigue syndrome. Am J Med 2000;108(2):99-105.

39. Zorenzenon M, Rukh G Botta GA et al. Ac- tive HHV-6 infection in chronic fatigue syn- drome patients from Italy: New data. J Chron Fatigue Syndrome 1996;2(4):3-12.

40. Jo Nijs J et al. High prevalence of Mycoplasma infections among European chronic fatigue syn- drome patients. Examination of four Mycoplasma species in blood of chronic fatigue syndrome pa- tients. FEMS Immunology & Medical Microbiol- ogy 2002;34: 209-214.

41. Nicolson G, Nicolson N. Diagnosis and treatment of Mycoplasmal Infections in Persian Gulf War Illness-CFIDS Patients. International Journal of Occupational Medicine, Immunology and Toxicology 1996;5:69-78.

42. Knox KK, Brewer JH, and Carrigan DR. Persistent active human herpesvirus six (HHV-6) infections in patients with chronic fatigue syndrome. J Chronic Fatigue Syndrome 1999;5:245-246.

43. Brewer JH, Know KK and Carrigan DR. Longitudinal study of chronic active human herpesvirus 6 (HHV-6) viremia in patients with chronic fatigue syndrome. Abstract. IDSA 37th Annual Meeting. Nov. 18-21, 1999. Philadelphia, Pennsylvania.

44. Ablashi DV et al. Human herpes virus and chronic fatigue syndrome. Canad Dis Weekly Rep 1991;17S1:33-40.

45. Josephs SF et al HHV-6 reactivation in chronic fatigue syndrome. Lancet 1991;1346-7.

46. Nicolson GL, Gan R, Haier J. Multiple co- infections (Mycoplasma, Chlamydia, human herpes virus-6) in blood of chronic fatigue syndrome patients: association with signs and symptoms. APMIS 2003;111(5):557-66.

47. Buchwald D. et al. A Chronic Illness Char- acterized by Fatigue, Neurological and Immu- nological Disorders, and Active Human Her- pesvirus Type 6 Infection. Annals of Internal Medicine 1992;116:103-113.

48. Martin W.J. Detection of viral related se- quences in CFS patients using the polymerase chain reaction.in “The Clinical and Scientific Basis of Myalgic Encephalomyelitis Chronic Fatigue Syndrome.” Byron M. Hyde Editor. Nightingale Research Foundation Press. Ottawa Canada pp 278-283, 1992.

49. Rowe PC, Bou-Holaigah I, Kan JS, Calkins H. Is NMH an Unrecognized Cause of Chronic Fatigue? Lancet 1995;345:623-4.

50. Naschitz JE, Rosner I, Rozenboum M et al. The head-up tilt test with haemodynamic insta- bility score in diagnosing chronic fatigue syn- drome. QJ Med 2003;96:133-142.

51. Gerrity TR, Bates J, Bell DS, Chrousos G, Furst G, Hedric T, Hurwitz B, Kula RW, Levine SM, Moore RC, Schondorf R. Chronic fatigue syndrome: what role does the autonomic ner- vous system play in the pathophysiology of this complex illness? NeuroImmunoModulation 2002;10:134-141.

52. Wallace DJ, Gallegua DS. Fibromyalgia: The Gastrointestinal Link. Current Pain and Head- ache Reports 2004;8:364–368.

53. Sivri A; Cindas A; Dincer F; Sivri B. Bow- el dysfunction and irritable bowel syndrome in fibromyalgia patients. Clin Rheumatol 1996;15(3):283-6.

54. Triadafilopoulos G; Simms RW; Goldenberg DL. Bowel dysfunction in fibromyalgia syn- drome. Dig Dis Sci 1991;36(1):59-64.

55. M Pimentel M, Wallace D, Hallegua D, Chow E, Kong Y, Park S, Lin HC. A link between irritable bowel syndrome and fibromyalgia may be related to findings on lactulose breath testing. Annals of the Rheumatic Diseases 2004;63:450-452.

56. Mark Pimentel et al.,Small Intestinal Bacte- rial Overgrowth: A Possible Association with Fibromyalgia, Journal of Musculoskeletal Pain 2001;9(3):107-113.

57. Berg D, Berg LH, Couvaras J, Harrison H. Chronic Fatigue Syndrome (CFS) &/or Fi- bromyalgia (FM) as a Variation of Antiphos- pholipid Antibody Syndrome (APS): An Ex- planatory Model and Approach to Laboratory Diagnosis of Blood Coagulation and Fibrinoly- sis 1999;10:1-4.

58. Berg D, Berg LH, Couvaras J. Is CFS/FM due to an undefined Hypercoaguable state brought on by immune activation of coagulation. Does adding anticoagulant therapy improve CFS/FM patient symptoms? AACFS Proceedings, Cam- bridge, MA, 10-12 October1998:62.

59. Berg D, Berg LH, Harrison H, Dreschsel. Retrospective study of 400+ CFS/FM patients for immune system activation of coagulation and hereditary coagulation defects as predispo- sition for CFS/FM. Proceedings International Society Thrombosis & Hemostasis July, 2001.

60. Harrison H, Ryser CA, , Brewer J, Berg D. Procoagulant Genetic Factors in a Pooled Cohort of 582 Chronic Fatigue Syndrome, Fibromyalgia and Related Chronic Illness Cases. VIIth Inter- national Conference American Association for Chronic Fatigue Syndrome (AACFS), Oct, 2004, Madison, WI, USA

61. Berg D, Berg LH, Harrison H. Low Level Ac- tivation of Coagulation with Coagulopathies in the Etiology of CFS / FM and Chronic Illnesses. An Explanatory Model Revisited. VIIth Inter- national Conference, American Association for Chronic Fatigue Syndrome (AACFS) Meeting, Madison, WI, Oct, 2004.

62. Harrison HH, Ryser CA, Ryser ME, et al. Use of sensitive markers of coagulation activa- tion to monitor low dose heparin therapy in patients with CFS and FM. Clinical Chemistry 2003;49(S6):A9.

63. Ojo-Amaize EA, Conley EJ, Peter JB. De- creased natural killer cell activity is associated with severity of chronic fatigue immune dys- function syndrome. Clin Infect Dis. 1994 Jan;18 Suppl 1:S157-9.

64. Gin W, Christiansen FT, Peter JB. Immune function and chronic fatigue syndrome. Med J Aust 1989:151:117-8.

65. Caligiuri M, Murray C, Buchwald D, et al. Phenotypic and functional deficiency of natural killer cells in patients with chronic fatigue syn- drome. J Immunol 1987:139:3306-13.

66. Stricker RB, Winger EE. Decreased CD57 lymphocyte subset in patients with chronic Lyme disease. Immunol Lett. 2001 Feb 1;76(1):43-8.

67. Klimas N, Salvato F, Morgan R, Fletcher M. Immunologic Abnormalities in Chronic Fatigue Syndrome. Journal of Clinical Microbiology, June 1990:1403-10.

68. Suhadolnik RJ et al. Biochemical evidence for a novel low molecular weight 2-5A-depen- dent RNase L in chronic fatigue syndrome. J In- terferon & Cytokine Res.1997;17:377-85.

69. Suhadolnik RJ et al. Biochemical dysregula- tion of the 2-5A synthetase/RNase L antiviral defense pathway in chronic fatigue syndrome. J Chronic Fatigue Syndrome.1999;5:223-242.

70. De Meirleir K et al. A 37 kDa 2-5 A binding protein as a potential biochemical marker for chronic fatigue syndrome. Am J Med.2000;108(2):99-105.

71. Suhadolnik RJ et al. Diagnosis of chronic fatigue syndrome (CFS): determination of a low molecular weight 37 kDa 2-5A dependent RNase L in peripheral blood mono-nuclear cell extracts. Second World Congress on Chronic Fatigue Syndrome and Related Disorders, Brus- sels, September 9-12, 1999.

72. Teitelbaum J, Bird B, Greenfield R, Weiss A, Muenz L, Gould L. Effective Treatment of Chronic Fatigue Syndrome (CFIDS) & Fibromy- algia (FMS) – A Randomized, Double-Blind, Pla- cebo-Controlled, Intent To Treat Study. Journal of Chronic Fatigue Syndrome 2001;8(2):3-28.

73. Blatman H. Effective Treatment of Fibro- myalgia and Myofascial Pain Syndrome: A Cli- nician’s Perspective. American Journal of Pain Management (Journal of the American Acad- emy of Pain Management) 2002;12(2):67-68.

74. Teitelbaum J. Effective Treatment of Chronic Fatigue Syndrome: Clinical Protocols and Prac- tice. Integrative Medicine 2005;4(4):CD-CG.

75. De Meirleir K, Englebienne P. Chronic Fa- tigue Syndrome: A Biological Approach. CRC Press. 2002.

76. International Association for Chronic Fatigue Syndrome (IACFS), Centers for Disease Control and Prevention (CDC) and the National Center for Infectious Diseases. Seventh International Conference on Chronic Fatigue Syndrome, Fi- bromyalgia and Other Related Illnesses. Octo- ber 8-10, Madison, Wisconsin 2004.

77. International Association for Chronic Fatigue Syndrome (IACFS), Centers for Disease Control and Prevention (CDC) and PANDORA. Eighth International Conference on Chronic Fatigue Syndrome, Fibromyalgia and Other Related Ill- nesses. Fort Lauderdale, FL Jan 12-14, 2007.

78. Latest 21st Century Advances in the Diag- nosis & Treatment of Fibromyalgia, Chronic Fatigue Syndrome and Related Illnesses. Los Angeles, CA Sept 19-21, 2002.

79. Ali M et al. Efficacy of ecologic-integrative management; protocols for reversal of fibromy- algia. J Integrative Medicine 1999;3:48-64.

80. Lowe JC, Reichman AJ, Yellin J. The process of change during T3 treatment for euthyroid fi- bromyalgia: a double-blind placebo-controlled crossover Study: Clinical Bulletin of Myofascial Therapy 1997;2(2/3):91-124.

81. PreAmerican Association for CFS/FMS 7th International Conference. A clinically focused workshop on Effective CFS/Fibromyalgia Thera- pies. October 7, 2004 Madison, Wisconsin.

82. Potential Unique etiologies of Chronic Fa- tigue Syndrome and Fibromyalgia: Hypercoa- guable State, Neurotoxins & Heavy Metals. Fifth Annual Fibromyalgia and Chronic Fatigue Con- ference. Kansas City, MO. Fibromyalgia Coali- tion International May 14, 2005.

83. Hormone Replacement Therapy in the Treat- ment of Fibromyalgia and CFIDS/Fibromyalgia CME Conference National Fibromyalgia Asso- ciation. Garden Grove, CA. May 18, 2006.

84. The Treatment of the Metabolic Consequenc- es of CFS/FM and Chronic Infections. American College for the Advancement of Medicine. Dal- las, TX. May 4, 2006.

85. Teitelbaum J. From Fatigue to Fantastic. Pen- guin Putnam Inc, 2001.

86. Holtorf K, Wightman W, Tenenbaum S, Shah P, White MD. Outcome database of 500+ CFS/ FM patients. Holtorf Medical Group Inc, Center for Hormone Imbalance, Hypothyroidismand Fatigue, Torrance, CA 2007.

87. Holtorf K, Wightman W, Tenenbaum S, Shah P, White MD, Spurlock M, Kippels K, LaBair A, Sharp L, Pierotti A, Bullington K, Garcia A, Ste- vens J, Sainer D, Campo A, Garabedian A, Marti L, Taveau S, Cuddapah S, Mustafa S, Stringer B, Boulden K, Bial E, Truong B, Elzinga L, Wazni G, Whitaker J, Cuddapah S, Lipschutz S, String- er DiGiovanni M, Levitz L, Hamp D, Juguilon F, Calabrese D, Zahoor I, Nurse-Bey H, Sidhwa Y, Shanti I, Littles C, Kelly L. Outcome database of 5000+ CFS/FM patients. Dallas TX, Fort Worth TX, Las Vegas NV, Salt Lake City UT, Portland OR, Seattle WA, Atlanta GA, Norwalk CT, Bos- ton MA, Philadelphia PA, Cleveland OH, Den- ver CO, Houston, TX, Detroit MI, Pittsburgh PA, Amarillo TX, Houston TX.

88. Wolfe F, Smythe HA, Yunus MB, Bennett RM, Bombardier C, Goldenberg DL, et al. The American College of Rheumatology 1990 crite- ria for the classification of fibromyalgia: report of the multicenter criteria committee. Arthritis Rheum 1990;33:160—72.

89. Katz RS, Wolfe F,2 Michaud K. Fibromyalgia Diagnosis: A Comparison of Clinical, Survey, and American College of Rheumatology Cri- teria. Arthritis & Rheumatism Vol. 54, No. 1, January 2006, pp 169–176

90. Wolfe F. Diagnosis of fibromyalgia. J Muscu- loskel Med 1990;7:53–69.

91. Aaron LA, Buchwald D. Chronic diffuse musculoskeletal pain, fibromyalgia and co-mor- bid unexplained clinical conditions. Best Pract Res Clin Rheumatol 2003;17:563–74.

92. Clauw DJ, Crofford LJ. Chronic widespread pain and fibromyalgia:What we know, and what we need to know. Best Pract Res Clin Rheumatol 2003;17:685–701.

93. Crofford LJ, Clauw DJ. Fibromyalgia: where are we a decade after the American Col- lege of Rheumatology classification criteria were developed? [editorial]. Arthritis Rheum 2002;46:1136–8.

94. Reeves WC, Lloyd A, Vernon SD, Klimas N, Jason LA, Bleijenberg G, Evengard B, White PD, Nisenbaum R, Unger ER, and the Interna- tional Chronic Fatigue Syndrome Study Group. Identification of ambiguities in the 1994 chronic fatigue syndrome research case definition and recommendations for resolution. BMC Health Services Research 2003;3:25.

95. Wearden AJ, Morriss RK, Mullis R, et al. Randomized, double-blind, placebo-controlled treatment trial of fluoxetine and graded exercise for chronic fatigue syndrome [published erra- tum appears in Br J Psychiatry 1998;173:89]. Br J Psychiatry 1998. 172:485-90.

96. Vercoulen JH, Swanink CM, Zitman FG, et al. Randomized, double-blind, placebo-controlled study of fluoxetine in chronic fatigue syndrome. The Lancet 1996;347:858-61.

97. Wolfe F, Anderson J, Harkness D, Bennett RM, Caro XJ, Goldenberg DL, Russell IJ, Yu- nus MB. Health status and disease severity in fibromyalgia: results of a six-center longitudinal study. Arthritis Rheum 1997 Sep;40(9):1571-9.

98. Andersen MM, Permin H, Albrecht F. Ill- ness and disability in Danish Chronic Fatigue Syndrome patients at diagnosis and 5-year follow-up. Journal of Psychosomatic Research 2004;56:217–229.

99. Joyce J, Hotopf M, Wessely S. The prognosis of chronic fatigue syndrome: a systematic re- view. Q J Med 1997;90(3):223-33.

100. Hoffman C, D. Rice D, Sung HY. Persons with chronic conditions. Their prevalence and costs. JAMA. Vol. 276 No. 18, November 13, 1996.

101. Levine PH et al. The Postinfectious Chronic Fatigue Syndrome. Humana Press, Clifton NJ 1989:405-38.

102. Deale A, Wessely S. Patients’ perceptions of medical care in chronic fatigue syndrome. Social Science & Medicine 2001;52:1859-1864.

103. Hinds GME, McCluskey DR. A retrospec- tive study of chronic fatigue syndrome. Proc Roy Coll Physicians, Edinburgh 1993; 23:10–14.

104. Peterson PK, Schenck CH, Sherman R. Chronic fatigue syndrome in Minnesota. Minne- sota Medicine 1991;74:21–6. Pain 1995;3:91–110.

105. Bennett RM: Fibromyalgia and the dis- ability dilemma. A new era in understanding a complex, multidimensional pain syndrome. Ar- thritis Rheum 1996;39:1627-1634.

106. Kennedy M, Felson DT. A prospective long- term study of fibromyalgia syndrome. Arthritis Rheum. 1996;39(4):682-5.

107. Wilson A et al. The treatment of chronic fa- tigue syndrome: science and speculation. Am J Med 1994;96(6):544-50.

108. Arnold LM, Rosen A, Pritchett YL, D’Souza DN, Goldstein DJ, Iyengar S, Wernicke JF. A randomized, double-blind, placebo-controlled trial of duloxetine in the treatment of women with fibromyalgia with or without major depres- sive disorder. Pain. 2005;119(1-3):5-15.

109. Barclay L, Vega C. Duloxetine Effective in Fibromyalgia. Medscape Medical News. Sept 10, 2004.

110. Crofford LJ, Rowbotham MC, Mease PJ, Russell J, Sworkin RH, et al. Pregabalin for the treatment of fibromyalgia. Arthritis and Rheu- matism 2005;52(4):1264-1273.

111. Nicolson G, Ellithorpe R. Lipid Replace- ment and Antioxidant Nutritional Therapy for Restoring Mitochondrial Function and Reduc- ing Fatigue in Chronic Fatigue Syndrome and other Fatiguing Illnesses. Journal of Chronic Fatigue Syndrome 2006;13(1):57-68.

112. Gebhart B. Benefit of Ribose in a Pa- tient with Fibromyalgia. Pharmacotherapy 2004;24(11):1646–1648)

113. Rossini M, Di Munno O, valentine G, Bi- anchi G, Biasi G, et al. Double-blind, multicenter trial comparing acetyl l-carnitine with placebo in the treatment of fibromyalgia patients. Clin Exp Rheumatol 2007;25(2): 182-8.

114. Teitelbaum JE, Johnson C, St Cyr J. The use of D-ribose in chronic fatigue syndrome and fi- bromyalgia: a pilot study. Altern Complement Med. 2006 Nov;12(9):857-62.

115. Massey PB. Reduction of fibromyalgia symptoms through intravenous nutrient ther- apy: results of a pilot clinical trial. Altern Ther Health Med. 2007;13(3):32-4.

116. Cox I. Red blood cell magnesium and chronic fatigue syndrome . The Lancet 1991;8744:757 –760.

117. Rose SR; Lustig RH; Pitukcheewanont P; Broome DC; Burghen GA; Li H; Hudson MM; Kun LE. Diagnosis of hidden central hypothy- roidism in survivors of childhood cancer. J Clin Endocrinol Metab 1999;84(12):4472-9.

118. Robin P. Peeters, Pieter J. Wouters, Hans van Toor, Ellen Kaptein, Theo J. Visser, and Greet Van den Berghe. Serum 3,3_,5_-Triiodothyro- nine (rT3) and 3,5,3_-Triiodothyronine/rT3 Are Prognostic Markers in Critically Ill Patients and Are Associated with Postmortem Tissue Deiodi- nase Activities. The Journal of Clinical Endocri- nology & Metabolism 90(8):4559–4565.

119. Annewieke W. van den Beld, Theo J. Vis- ser, Richard A. Feelders, Diederick E. Grobbee, and Steven W. J. Lamberts Thyroid Hormone Concentrations, Disease, Physical Function, and Mortality in Elderly Men. J Clin Endocrinol Me- tab 2005;90: 6403-6409.

120. Robin P. Peeters, Serge van der Geyten, Pieter J. Wouters, Veerle M. Darras, Hans van Toor, Ellen Kaptein, Theo J. Visser, and Greet Van den Berghe. Tissue Thyroid Hormone Lev- els in Critical Illness. J Clin Endocrinol Metab 2005;90:6498-6507.

121. Lowe J, Garrison R, Reichman A, MD, Yellin J, Thompson BA, Kaufman D. Effective- ness and safety of T3 (triiodothyronine) thera- py for euthyroid fibromyalgia: a double-blind placebo-controlled response-driven crossover study.: Clinical Bulletin of Myofascial Therapy 1997;2(2/3):31-58.

122. Lowe JC, Reichman AJ, Garrison R, Yellin J. Triiodothyronine (T3) treatment of euthyroid fibromyalgia: a small-n replication of a double- blind placebo-controlled crossover study. Clinical Bulletin of Myofascial Therapy 1997;2(4):71-88.

123. Yellin BA, Reichman AJ, Lowe JC. The Pro- cess of Change During T3 Treatment for Euthy- roid Fibromyalgia: A Double-Blind Placebo-Con- trolled Crossover Study. The Metabolic Treatment of Fibromyalgia. McDowell Publishing 2000.

124. Moorkens G, Wynants H, Abs R: Effect of growth hormone treatment in patients with chronic fatigue syndrome: a preliminary study. Growth Horm IGF Res 1998;8(B):131-133.

125. Nicolson, G, Marwan Y. Nasralla M, De Meirleir K, J Haier. Bacterial and Viral Co-Infec- tions in Chronic Fatigue Syndrome (CFS/ME) Patients. Proc. Clinical & Scientific Conference on Myalgic Encephalopathy/Chronic Fatigue Syndrome, the Practitioners Challenge, Alison Hunter Foundation, Sydney, Australia 2002.

126. Lerner AM, Zervos M and Chang CH et al. A small, randomized, placebo-controlled trial of the use of antiviral therapy for patients with chronic fatigue syndrome. Clinical Infectious Diseases 2001;32:1657-58.

127. Nicolson, G. L., Nasralla, M. Y. , Franco, R, A., Nicolson, N. L., Erwin, R., Ngwenya, R. &, and Berns, P.A. Clinical Practice of Alternative Medicine 2000;1(2):92-102.

128. Montoya et al. Use of valganciclovir (Val- cyte) in patients with elevated antibody titers against Human Herpesvirus-6 (HHV-6) and Epstein-Barr Virus (EBV) who were experienc- ing central nervous system dysfunction includ- ing long-standing fatigue. Journal of Clinical Virology 2006;37:S33-38.

129. Shoemaker, R. C., Hudnell, H. K. 2001, “Pos- sible Estuary Associated Syndrome: symptoms, vision and treatment”, Environmental Health Perspectives ; 109(5): 539-545.

130. Shoemaker, R. C. 2000, “Poster H05, Treat- ment of Possible Estuarine Associated syn- drome: Neurotoxins, contrast sensitivity and cholestyramine”, CDC National Conference on Pfiesteria: From Biology to Public Health 10/18-10/20/2000, Stone Mountain, Georgia.

131. Shoemaker RC. Residential and recreational acquisition of Possible Estuary Associated Syn- drome: a new approach to successful diagnosis and treatment, Environmental Health Perspec- tives 2001;109(S5): 791-796.

Get In Touch With Us

Contact Info

2 Comment

elder massage therapy in nursing home in Linden

kompas update